Serum Cathepsin S Is Associated with Decreased Insulin Sensitivity and the Development of Diabetes Type 2 in a Community Based Cohort of Elderly Men

Postprint This is the accepted version of a paper published in Diabetes Care. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men. Access to the published version may require subscription. Abstract Objective To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes. Research design and Methods Serum cathepsin S, insulin sensitivity (euglycaemic hyperinsulinaemic clamp) and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in Uppsala Longitudinal Study of Adult Men (mean age 71 years, n=905). Thirty participants developed diabetes during 6 years follow-up. Results After adjustment for age, anthropometric variables and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase-0.09, 95% CI,-0.14-0.04 p=0.001) while no association with early insulin response was found. Moreover, higher cathepsin S was associated with higher risk for developing diabetes (odds ratio per SD increase 1.48, 95 % CI 1.08-2.01, p=0.01). Conclusions Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.